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Preliminary Study On The Role Of Septin9 Mediates Epithelial-mesenchymal Transition In Development And Prognosis Of Cervical Squamous Cell Carcinoma

Posted on:2020-11-21Degree:MasterType:Thesis
Country:ChinaCandidate:G P LiuFull Text:PDF
GTID:2404330572978193Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Objective:The Septin9 protein encoded by the SEPT9 gene is a cytoskeletal protein with complex functions.Recently,SEPT9 has been closely related to tumors and has become a new hotspot in the study of molecular mechanisms of tumors.However,its role in the development of cervical squamous cell carcinoma has not been reported.In this study,we examined the expression of Septin9 in normal cervical tissues,CIN lesions,and cervical squamous cell carcinoma,to explore the possible role of Septin9 in the development of cervical squamous cell carcinoma.Simultaneous the expression of Vimentin and E-cadherin in cervical squamous cell carcinoma were detected,the relationship between Septin9,Vimentin and E-cadherin protein and clinicopathological features of cervical squamous cell carcinoma was analyzed,to explore the relationship between SEPT9 and epithelial-mesenchymal transition-related proteins and its possible mechanism Septin9 as a cytoskeletal protein involved in the invasion,metastasis and prognosis of cervical squamous cell carcinoma.Method:50 samples of cervical squamous cell carcinoma with differentiation of different degrees from the patients who received surgical resection in the First People's Hospital of Nei Jiang were selected retrospectively from July 2010 to July 2012,another 20 samples of normal cervical tissue samples from the patients who received the surgical of removal of the uterus with uterine leiomyomas were selected as negative control,20 samples of CINI grade specimens and 20 cases of CIN?-? specimens were selected else;at the same time,the clinical and pathological data of patients with cervical squamous cell carcinoma were collected and arranged,survival within 5 years were followed up;the immunohistochemical En Vision method was used to detect the expression of Septin9 in all selected normal cervical tissues,CINI grade,CINII-? grade and cervical squamous cell carcinoma tissues,and the expression of Vimentin and E-cadherin in cervical squamous cell carcinoma was detected by the same method;at the same time,the patients with tumor thrombus,extra-cervical invasive metastasis and/or lymph node metastasis were classified as high metastasis and recurrence tendency group,then those patients without tumorthrombus,extracervical invasive metastasis and/or lymph node metastasis were classified as low metastasis recurrence tendency group;to analyze therole of Septin9 in the development of cervical cancer and the relationship between the expression of Septin9 and Vimentin,E-cadherin and the relationship between the expression of Septin9,Vimentin,E-cadherin and clinicopathological features and prognosis of patients with cervical cancer by combing with clinical data such as age,differentiation,lymph node metastasis,depth of invasion,FIGO stage,vascular tumor thrombus,parametrial infiltration,and follow-up results,etc.Results:(1)The positive rates of Septin9 in normal cervical tissue,CINI grade,CIN?-? grade and cervical squamous cell carcinoma were 10%?100%,95%,94%,respectively,The positive rate of Septin9 in CINI grade,CIN?-? grade and cervix squamous cell carcinoma was significantly higher than that in normal cervical tissues(P<0.01);There was no significant difference in Sept.in9 positive rate and positive intensity between CINI grade,CIN?-? grade and cervical squamous cell carcinoma(P>0.05).(2)The strong positive rates of Septin9 in cervical cancer patients with lymph node metastasis and vascular tumor thrombus(71.5%,81.8%,respectively)were significantly higher than those in cervical cancer patients without lymph node metastasis and vascular tumor thrombus(63.9%,35.9%,respectively),respectively(P<0.01 or 0.05).(3)There was statistically significant difference in the positive rates of E-cadherin,which were 100%,50%,and 11.8%in high,moderate and poorly differentiated squamous cell carcinoma,respectively,(P<0.01);the positive rate of E-cadherin in patients with lymph node metastasis and vascular tumor thrombosis(14.3%,0%,respectively)was significantly lower than that in patients without lymph node metastasis and vascular tumor thrombosis(58.3%,59.0%)respectively(P<0.05 or 0.01).there was statistically significant difference in the positive rates of Vimentin,which were11.1%,37.5%,and 82.4%in high,moderate and poorly differentiated squamous cell carcinoma,respectively(P<0.01).The positive rate of Vimentin in patients with lymph node metastasis(78.6%)was significantly higher than that in patients without lymph node metastasis(36.1%)(P<0.05).(4)Comparison of the expression of Septin9,E-cadherin and Vimentin in the high metastasis and recurrence tendency group and the low metastasis and recurrence tendency group showed that the positive rate of E-cadherin in the high metastasis recurrence tendency group(21.1%)was lower than that in the low metastasis recurrence tendency group(61.3%)(P<0.05);the positive rate of Vimentin in high metastasis and recurrence tendency group(73.7%)was significantly higher than low metastasis recurrence tendency group(32.3%)(P<0.01);the strong positive rate of Septin9 in high metastatic recurrence tendency group(78.9%)was significantly higher than that in the low metastasis and recurrence tendency group(25.8%)(P<0.01).(5)Kendall's tau-b correlation analysis showed that the expression of Septin9 was negatively correlated with the expression of E-cadherin(r=-0.312,P<0.05),and positively correlated with the expression of Vimentin(r=0.301,P<0.05)in cervical squamous cell carcinoma.(6)COX proportional hazard regression analysis showed that parametrial infiltration and vascular tumor thrombus were risk factors for death in cervical cancer patients(P<0.05),The risk of death in patients with parametrial infiltration was 20.767 times than that of patients without parametrial infiltration;The risk of death in patients with vascular tumor thrombus was 9.718 times than that of patients without vascular tumor thrombus;the other factors were not statistically significant(P>0.05)Conclusions:(1)The expression of Septin9 in CINI,CIN?-? and cervical squamous cell carcinoma was significantly higher than that in normal cervical tissues,suggesting that SEPT9 may be involved in the development of cervical squamous cell carcinoma,which may play the role of oncogene.(2)Compared with the low metastasis and recurrence tendency group(cervical cancer patients without tumor thrombus,extracervical infiltration,and/or lymph node metastasis),the expression of Septin9 protein in the high metastasis and recurrence tendency group(cervical cancer patients with tumor thrombus,extracervical infiltration,and/or lymph node metastasis)was more likely to strongly positive,which suggest that SEPT9 may be involved in promoting cervical cancer invasion and metastasis.(3)The expression of Septin9 protein was negatively correlated with the expression of E-cadherin protein,and positively correlated with the expression of Vimentin protein in cervical squamous cell carcinoma,suggesting that SEPT9 may mediate EMT and promote cervical cancer metastasis.(4)There is a correlation between the expression levels of E-cadherin and Vimentin with degree of differentiation of cervical squamous cell carcinoma and the tumor cell invasiveness and metastasis.(5)The analysis of COX risk regression model showed that expression of Septin9 and E-cadherin and Vimentin in cervical squamous cell carcinoma were not independent risk factors for the prognosis of cervical cancer patients,Septin9 may be only one of the factors that promote the invasion and metastasis of cervical cancer cells.and its value in prognosis evaluation needs further study.
Keywords/Search Tags:Cervical squamous cell carcinoma, SEPT9, E-cadherin, Vimentin, oncogene, invasion and metastasis
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